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Microbes & Immunity Regulation of Staphylococcus aureus CP biosynthesis
cause not only skin and soft tissue infection, bronchitis, resulting in complex and diverse CP structures, with
pneumonia, endocarditis, and brain abscess but also lead to molecular weight ranging from 100 to 2,000 kDa. Among
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food poisoning, exfoliative dermatitis, and toxin-mediated the 13 S. aureus CP serotypes, only five types (CP1, CP2,
diseases. In the United States, mortality due to S. aureus CP4, CP5, and CP8) have been structurally characterized
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infections exceeds that of acquired immunodeficiency (Figure 1A). S. aureus CPs are primarily composed of rare
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syndrome and viral hepatitis. In China, S. aureus remains monosaccharide units. In 1974, Liau et al. identified three
the most frequently isolated Gram-positive bacterial key components in CP1 strain M: Taurine, 2-acetamido-
pathogen in clinical settings. According to the 2023 2-deoxy-α-D-galactopyranosyluronic acid, and N-acetyl-
CHINET surveillance report (http://www.chinets.com), D-fucosamine (D-FucNAc). The complete CP1 structure
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S. aureus accounted for 9.23% of all clinical isolates, was elucidated in 1983 by Murthy et al., who determined
ranking as the third most prevalent bacteria after the its repeating unit, with taurine covalently linked through
Gram-negative Escherichia coli (18.11%) and Klebsiella amide bonds to every fourth GalNAcA residue. Notably,
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pneumoniae (14.22%). a CP1 variant (strain D), identified in 1982, shares the same
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Virulence factors are the weapons by which a bacterium polysaccharide backbone but lacks taurine modifications.
causes disease. S. aureus can produce a variety of virulence The full structure of S. aureus CP2 was determined
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factors, such as hemolysins, enterotoxins, exfoliative in 1964. This capsular polymer contains equimolar
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toxins, and toxic shock syndrome toxins. Capsule is amounts of 2-acetamido-2-deoxy-D-glucuronic acid
5,7
also an important virulence factor of S. aureus. In 1931, (D-GlcNAcA) and 2-(N-acetylalanylamino)-2-deoxy-D-
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Gilbert first reported that the capsule plays a vital role glucuronic acid units, linked through β-(1→4) glycosidic
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in the pathogenesis of S. aureus, and accumulated data bonds. S. aureus CP4 consists of a repeating disaccharide
have revealed that more than 90% of clinical S. aureus unit of 2-acetamido-2-deoxy-D-mannopyranuronic
isolates produce capsules. Although the structure, acid (D-ManNAcA) and D-FucNAc with a β-(1→3)
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biosynthesis, function, and regulation of S. aureus capsular glycosidic linkage. The overall structure of CP5 was first
polysaccharides (CPs) have been reviewed, 11-14 significant characterized in 1990 as a repeating trisaccharide unit
progress has been made in recent years. For instance, the and revised in 2005 to the corrected structure: →4)-β-D-
known functions of S. aureus capsule have expanded to ManNAcA-(1→4)-α-L-FucNAc(3-OAc)-(1→3)-β-D-
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include protection against phagocytosis, inhibition of FucNAc-(1→. In contrast, the revised chemical structure
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neutrophil chemotaxis, promotion of bacterial adhesion of CP8 was established by Jones (2005), who described
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and colonization, resistance to phage adsorption, and a repeating trisaccharide unit in S. aureus strain Becker:
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stimulation of antibody production. 18 →3)-β-D-ManNAc(4-OAc)-(1→3)-α-L-FucNAc-(1→3)-α-
D-FucNAc-(1→. 11,20
Based on immunological specificity, monosaccharide
composition, and glycosidic linkage of CPs, S. Morphologically, colonies of S. aureus with CP1 and
aureus capsules are classified into 13 serotypes (CP1 – CP2 are mucoid, indicating rich capsule production. In
CP13). 14,19-21 Notably, epidemiological investigations have contrast, the colonies formed by CP3–CP13 S. aureus
revealed that more than 80% of clinically significant isolates are non-mucoid, and their capsules are not readily
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S. aureus strains carry CP5 or CP8. This review observed. To date, the precise chemical structures of
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comprehensively examines S. aureus capsule biology, additional S. aureus CP types remain uncharacterized due
covering: (i) structural and functional characteristics, to their rare clinical isolation.
(ii) biosynthetic pathways, mainly for CP5 and CP8, The majority of clinical S. aureus isolates carry CP5
(iii) genetic and environmental regulation, and (iv) CP or CP8. In Mexico, 262 clinical methicillin-resistant
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preparation methods. The integrated information provides S. aureus (MRSA) strains were isolated, of which 93.5%
a valuable resource for future research on capsule-mediated were characterized as CP5 and the remainder as CP8.
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pathogenesis and potential therapeutic targets. Mohamed et al. analyzed 506 clinical S. aureus isolates and
2. Structure and function of S. aureus found that 72% strains carried CP5 and 28% possessed
CP8. Similarly, Shi et al. reported that in dairy goats
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capsule across China, CP5 accounted for 52.5% and CP8 for
The S. aureus capsule is a linear polysaccharide 47.5% of S. aureus isolates strains. The reason for the
structurally composed of amino-hexuronic acid and higher prevalence of CP5 over CP8 in clinical settings
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oligosaccharide repeat units. In general, the glycosidic remains unclear. Bardiau et al. revealed that CP8-positive
linkages of monosaccharides and the number of repeating S. aureus strains exhibited a lower invasion rate than CP5-
oligosaccharide units vary among S. aureus strains, positive strains. Structurally, the main difference between
Volume 2 Issue 4 (2025) 2 doi: 10.36922/mi.8392

